Neonatal hyperammonemia and citrullinemia caused by argininosuccinate lyase gene mutations

Abstract

Objective To analyze the characteristics of neonatal hyperammonemia and citrullinemia caused by argininosuccinate lyase (ASL) gene mutations, and to have a better understanding of this disease. Methods A neonatal patient with the onset of hyperammonemia and citrullinemia admitted to the Department of Pediatrics of Peking University First Hospital on April 2, 2014, was retrospectively studied. Peripheral blood leukocyte DNA of the patient and his parents was collected to detect ASS1, ASL and SLC25A13 gene mutations. The literature related to neonatal hyperammonemia, citrullinemia and argininosuccinic aciduria was reviewed. Results The baby in this case appeared lethargic, had weaker crying and food refusal since three days after birth, and analysis of blood amino acid found a marked increase in blood ammonia (1 332 μmol/L) and a significant rise in citrulline (759.12 μmol/L). Sanger sequencing detection revealed compound heterozygous mutations in the ASL gene (c.434 A>G, c.857A>C) and this c.857A>C mutation was the first reported case in China. This case of hyperammonemia and citrullinemia was confirmed as argininosuccinic aciduria caused by ASL gene mutations. A protein-limited diet and the treatment of arginine and L-carnitine were given. His blood ammonia decreased to normal level and there was a significant improvement in physical and intellectual progress at five months old. Unfortunately, he had an intestinal infection when he was over five months old and the blood ammonia level tested in the local hospital was 480 μmol/L. Gradually there was a disturbance of consciousness, then coma, and he finally died after active rescue in the local hospital. Conclusions Hyperammonemia and citrullinemia in neonates are likely to be argininosuccinic aciduria and a gene mutation test may be helpful for diagnosis. Key words: Hyperammonemia; Citrullinemia; Argininosuccinate lyase; Argininosuccinic aciduria; Mutation; Infant, newborn